Objective To explore the effect of curcumin(CUR)on oxidative damage of keratinocytes induced by ultraviolet B(UVB)irradiation through Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/nucleotide-binding oligomerization domain-containing protein 3(NLRP3)signaling pathway.Methods Human keratinocytes of HaCaT were cultured normally in vitro,and the keratinocyte oxidative damage model was established by the irradiation of 57 mJ/cm2 UVB.The cells with normal culture were as the control group,the cells treated after modeling were as the UVB group,the cells treated with 5 μmol/L CUR after modeling were as the CUR group,the cells treated with 100 μg/L TLR4 inhibitor of TAK-242 after modeling were as the TAK-242 group,and the cells treated with 5 μmol/L CUR and 100 nmol/L TLR4 activator of lipopolysaccharide(LPS)were as the CUR+LPS group.qRT-PCR was applied to detect the relative expression levels of TLR4,NF-κB,and NLRP3 mRNAs of cells in each group.CCK-8 was applied to detect the cell proliferation in each group.The relative content of reactive oxygen species(ROS),the viabilities of superoxide dismutase(SOD)and catalase(CAT),and the concentrations of glutathione(MDA)and glutathione(GSH)of cells in each group were detected by fluorescence assay according to the kit instruction.ELISA kit was used to detect the expression of inflammatory factors of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)of cells in each group.Flow cytometry was applied to detect the cell apoptosis in each group.Western blot was applied to detect the expression of proliferation related protein of proliferating cell nuclear antigen(PCNA),apoptosis related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)],and TLR4/NF-κB/NLRP3 signaling pathway related proteins(TLR4,NF-κB and NLRP3)of cells in each group.Results Compared with the Control group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the UVB group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Compared with the UVB group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the TAK-242 group and CUR group increased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 decreased(P<0.05).Compared with the CUR group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the CUR+LPS group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Conclusion CUR can increase the antioxidant stress level of keratinocytes,alleviate inflammatory response,promote cell proliferation,and improve cell damage caused by UVB irradiation,which may be related to the inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

Objective To explore the effect of curcumin(CUR)on oxidative damage of keratinocytes induced by ultraviolet B(UVB)irradiation through Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/nucleotide-binding oligomerization domain-containing protein 3(NLRP3)signaling pathway.Methods Human keratinocytes of HaCaT were cultured normally in vitro,and the keratinocyte oxidative damage model was established by the irradiation of 57 mJ/cm2 UVB.The cells with normal culture were as the control group,the cells treated after modeling were as the UVB group,the cells treated with 5 μmol/L CUR after modeling were as the CUR group,the cells treated with 100 μg/L TLR4 inhibitor of TAK-242 after modeling were as the TAK-242 group,and the cells treated with 5 μmol/L CUR and 100 nmol/L TLR4 activator of lipopolysaccharide(LPS)were as the CUR+LPS group.qRT-PCR was applied to detect the relative expression levels of TLR4,NF-κB,and NLRP3 mRNAs of cells in each group.CCK-8 was applied to detect the cell proliferation in each group.The relative content of reactive oxygen species(ROS),the viabilities of superoxide dismutase(SOD)and catalase(CAT),and the concentrations of glutathione(MDA)and glutathione(GSH)of cells in each group were detected by fluorescence assay according to the kit instruction.ELISA kit was used to detect the expression of inflammatory factors of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)of cells in each group.Flow cytometry was applied to detect the cell apoptosis in each group.Western blot was applied to detect the expression of proliferation related protein of proliferating cell nuclear antigen(PCNA),apoptosis related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)],and TLR4/NF-κB/NLRP3 signaling pathway related proteins(TLR4,NF-κB and NLRP3)of cells in each group.Results Compared with the Control group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the UVB group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Compared with the UVB group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the TAK-242 group and CUR group increased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 decreased(P<0.05).Compared with the CUR group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the CUR+LPS group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Conclusion CUR can increase the antioxidant stress level of keratinocytes,alleviate inflammatory response,promote cell proliferation,and improve cell damage caused by UVB irradiation,which may be related to the inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To understand the clinical application of magnesium sulfate injection in inpatients of the obstetrical department, and analyze retrospectively its rationality and existing problems.Methods:The clinical data of obstetric inpatients who used magnesium sulfate injection in the hospital information system of our hospital from September 2022 to January 2023 were collected. Based on the drug instructions, guidelines for the diagnosis and treatment of hypertensive disorders in pregnancy, domestic and foreign guidelines, and literature reports, the rationality of magnesium sulfate injection in terms of obstetric medication indications, dosage and administration, and treatment course was evaluated.Results:A total of 303 obstetric patients were included in the use of magnesium sulfate injection, with an age of 32 (ranging from 18 to 44) years and a gestational age of 14 to 40 weeks. Among them, 33 cases were used for threatened abortion, 141 cases for threatened preterm birth, and 129 cases for the prevention of eclampsia attacks. Among the 303 patients, 134 cases (44.22%) had no indications for medication. Among them, 13 patients with threatened abortion were treated for fetal brain protection, and 20 patients with threatened abortion and 101 patients with threatened preterm birth were treated for preventing miscarriage by uterine contraction inhibition. There were 118 cases (38.94%) with inappropriate administration methods, mainly due to inappropriate usage and dosage, as well as overly long treatment courses. Of them, 26 cases (22.03%, 26/118) used for brain protectors of premature fetuses were not given loading doses, 15 (12.71%, 15/118) cases had a total medication duration of more than 48 hours, 76 cases (64.41%, 76/118) used for the prevention of eclampsia were not given loading dose, and 1 case (0.85%, 1/118) received rapid infusion time of the loading dose more than 30 minutes. Among the 303 patients, 3 patients presented nausea and vomiting, constipation, and skin flushing, respectively.Conclusions:Nearly half of the magnesium sulfate injection used in obstetrics department in our hospital has inappropriate indications and over one-third has non-standard usage, dosage, and treatment courses. Clinicians should comprehensively assess the patient′s condition and strictly follow recommended methods in the guidelines and drug instructions for standardized use.

Objective To investigate the therapeutic effect of hypericin on acute pancreatitis(AP)in mice and its effect on NLRP3 inflammasome signaling pathway.Methods The AP model in mice was established with caerulein(CER).The mice were divided into the normal control group,the model group(AP group),the low-dose HY group(CER+HY 5 mg/kg group),the medium-dose HY group(CER+HY 10 mg/kg group)and the high-dose HY group(CER+HY 20 mg/kg group),with 10 mice in each group.The 266-6 mouse pancreatic acinar cancer cells were treated with cholecystokinin(CCK)and divided into the control group,the AP group,the CCK+HY 1 μmol/L group,the CCK+HY 2 μmol/L group and the CCK+HY 4 μmol/L group.The activities of amylase(AMS),lipase,trypsin and myeloperoxidase(MPO)in the serum of each group of mice,and levels of inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay(ELISA).The expression of NOD-like receptor family protein 3(NLRP3)was detected by Western blot assay.The mRNA levels of NLRP3,caspase(Caspase)-1,IL-1β,TNF-α and IL-18 in pancreatic tissue of mice were detected by real-time quantitative PCR(q-PCR).The cell survival rate of cells in each group was detected by CCK8 method.The mRNA expression levels of NLRP3,Caspase-1 and IL-18 in each group of cells were detected by q-PCR.Results Compared with the normal control group,the levels of AMS,lipase,MPO,trypsin,IL-1β and TNF-α in serum of the model group,and the mRNA and protein expression levels of NLRP3,IL-1β,TNF-α,IL-18 and Caspase-1 in pancreatic tissue were increased(P＜0.01).Compared with the model group,the levels of AMS,IL-1β and TNF-α,the enzymatic activity of trypsin in serum,and the mRNA levels of IL-1β,TNF-α,IL-18 and Caspase-1 in pancreatic tissue were decreased in the low-,medium-and high-dose HY groups.The serum levels of lipase and MPO and the mRNA expression levels of NLRP3 in pancreatic tissue were decreased in the medium-and high-dose HY groups(P＜0.05).Compared with the AP group,the cell survival rates were increased in the CCK+HY 1 μmol/L group,the CCK+HY 2 μmol/L group and the CCK+HY 4 μmol/L group,and the mRNA levels of NLRP3,IL-18 and Caspase-1 were decreased in a dose-dependent manner(P＜0.05).Conclusion Hypericin can effectively treat AP in vivo and in vitro,and its therapeutic effect may be related to the regulation of NLRP3 inflammasome signaling pathway.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective To investigate the role of Sneathia sanguinegens(S.sanguinegens)in the development of unexplained recurrent spontaneous abortion(URSA).Methods A case-control study was conducted to analyze the vaginal flora characteristics of 65 patients with URSA and 18 healthy controls through 16S rRNA gene sequencing.Toxicity profile of S.sanguinegens on human cervical cancer cells(ME-180),human umbilical vein endothelial cells(HUVEC)and human placental choriocarcinoma cells(JEG-3)was analyzed at the cellular level to assess the mechanism of it in adverse pregnancy outcomes.And S.sanguinegens was used to infect C57BL/6J mice to explore the toxic effect on living organisms.Results The relative abundance of Sneathia was increased in patients with URSA compared with healthy controls.It was positively correlated with the number of miscarriages,and was attributed to S.sanguinegens.We also found that S.sanguinegens damaged ME-180,JEG-3 and HUVEC cells.The degree of cellular damage was related to the level of S.sanguinegens added.Intravenous infection with S.sanguinegens caused inflammatory damage in several organs and extramedullary hematopoiesis in the spleen.Conclusion S.sanguinegens is closely related to URSA and should be emphasized in patients with high vaginal bacterial load.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective To investigate the therapeutic effect of hypericin on acute pancreatitis(AP)in mice and its effect on NLRP3 inflammasome signaling pathway.Methods The AP model in mice was established with caerulein(CER).The mice were divided into the normal control group,the model group(AP group),the low-dose HY group(CER+HY 5 mg/kg group),the medium-dose HY group(CER+HY 10 mg/kg group)and the high-dose HY group(CER+HY 20 mg/kg group),with 10 mice in each group.The 266-6 mouse pancreatic acinar cancer cells were treated with cholecystokinin(CCK)and divided into the control group,the AP group,the CCK+HY 1 μmol/L group,the CCK+HY 2 μmol/L group and the CCK+HY 4 μmol/L group.The activities of amylase(AMS),lipase,trypsin and myeloperoxidase(MPO)in the serum of each group of mice,and levels of inflammatory factors interleukin(IL)-1β and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay(ELISA).The expression of NOD-like receptor family protein 3(NLRP3)was detected by Western blot assay.The mRNA levels of NLRP3,caspase(Caspase)-1,IL-1β,TNF-α and IL-18 in pancreatic tissue of mice were detected by real-time quantitative PCR(q-PCR).The cell survival rate of cells in each group was detected by CCK8 method.The mRNA expression levels of NLRP3,Caspase-1 and IL-18 in each group of cells were detected by q-PCR.Results Compared with the normal control group,the levels of AMS,lipase,MPO,trypsin,IL-1β and TNF-α in serum of the model group,and the mRNA and protein expression levels of NLRP3,IL-1β,TNF-α,IL-18 and Caspase-1 in pancreatic tissue were increased(P＜0.01).Compared with the model group,the levels of AMS,IL-1β and TNF-α,the enzymatic activity of trypsin in serum,and the mRNA levels of IL-1β,TNF-α,IL-18 and Caspase-1 in pancreatic tissue were decreased in the low-,medium-and high-dose HY groups.The serum levels of lipase and MPO and the mRNA expression levels of NLRP3 in pancreatic tissue were decreased in the medium-and high-dose HY groups(P＜0.05).Compared with the AP group,the cell survival rates were increased in the CCK+HY 1 μmol/L group,the CCK+HY 2 μmol/L group and the CCK+HY 4 μmol/L group,and the mRNA levels of NLRP3,IL-18 and Caspase-1 were decreased in a dose-dependent manner(P＜0.05).Conclusion Hypericin can effectively treat AP in vivo and in vitro,and its therapeutic effect may be related to the regulation of NLRP3 inflammasome signaling pathway.